Flow-Enabled, Modular Access to α,α-Difluoromethylene Amines.

ABSTRACT: The α,α-difluoromethylene amine (NCF₂R) motif represents a useful functionality in medicinal chemistry, yet practical and modular methods to access this class of compounds are lacking. Here, we report a safe and scalable flow-based strategy for the on-demand generation of NCF₂R anions using a packed-bed microreactor containing caesium fluoride. This protocol enables the late-stage installation of the CF₂ group under mild conditions, avoiding the use of hazardous fluorinating agents and minimizing fluorinated waste. This fully modular strategy features three points of diversification (carboxylic acid, sulfonamide, and electrophile), allowing efficient access to a broad range of α,α-difluoromethylene amines. The method tolerates a variety of functional groups

SUBMITTER: Nagornii D 

PROVIDER: S-EPMC12723450 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature